Journal
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
Volume 13, Issue 1, Pages 92-102Publisher
SPRINGERNATURE
DOI: 10.1039/c3pp50226k
Keywords
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Funding
- Russian Foundation for Basic Research [10-04-01436, 13-04-00670]
- M.V. Lomonosov Moscow State University Program of Development
- User Facilities Center of M.V. Lomonosov Moscow State University [16.552.11.7081]
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Further development of boron neutron capture therapy (BNCT) requires new neutronsensitizers with improved ability to deliver B-10 isotopes in cancer cells. Conjugation of boron nanoparticles with porphyrin derivatives is an attractive and recognized strategy to solve this task. We report on breakthroughs in the structural optimization of conjugates of chlorin e(6) derivative with cobalt-bis(dicarbollide) nanoparticles resulting in the creation of dimethyl ester 13-carbomoylchlorin e(6) [ N-hexylamine-N'-ethoxyethoxy]cobalt-bis(dicarbollide) (conjugate 1). Conjugate 1 is able to accumulate quickly and efficiently (distribution factor of 80) in cancer cells, thus delivering more than 109 boron atoms per cell when its extracellular concentration is more than 1 mol L-1. Also 1 is an active photosensitizer and is phototoxic towards human lung adenocarcinoma A549 cells at 80 nmol L-1 (50% cell death). Photoinduced cytotoxicity of 1 is associated with lipid peroxidation, lysosome rupture and protease activity enhancement. Conjugate 1 fluoresces in the red region (670 nm), which is useful to monitor its accumulation and distribution in vivo. It is not toxic to cells without activation by neutrons or photons. Structural features that improve the functional properties of 1 are discussed. The properties of 1 warrant its preclinical evaluation as a multifunctional agent for BNCT, photodynamic therapy and fluorescent tumor diagnosis.
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